Hypothalamic-pituitary-adrenal axis dysfunction in Alzheimer's disease: lack of association between longitudinal and cross-sectional findings.
OBJECTIVE
The authors examined longitudinal hypothalamic-pituitary-adrenal (HPA) axis function in Alzheimer's disease.


METHODS
Cortisol levels of 30 patients with Alzheimer's disease and 17 healthy elderly subjects were measured before and after administration of dexamethasone. These measures were repeated at 9-month intervals in the patients with Alzheimer's disease.


RESULTS
At baseline, cortisol levels were higher in the Alzheimer's disease group before and after dexamethasone administration. Although only two of the four patients whose cortisol levels were not suppressed by dexamethasone also had high cortisol levels before dexamethasone administration, basal and postdexamethasone cortisol levels were correlated. HPA axis dysfunction correlated with severity of dementia at baseline but was not stable longitudinally and did not increase with follow-up.


CONCLUSIONS
There was no association between longitudinal and cross-sectional findings. The longitudinal data were not consistent with a role for the glucocorticoid cascade hypothesis (that hippocampal cell loss in Alzheimer's disease results in hypercortisolism, which in turn acts as a co-factor in further degeneration) in the pathophysiology of mild and moderate Alzheimer's disease.
Swanwick
G R
GR
Mercer's Institute for Research on Ageing, St. James's Hospital, Dublin, Ireland.
Kirby
M
M
Bruce
I
I
Buggy
F
F
Coen
R F
RF
Coakley
D
D
Lawlor
B A
BA
D000368:Aged; D000544:Alzheimer Disease / Q000097:blood / Q000175:diagnosis / Q000503:physiopathology*; D003430:Cross-Sectional Studies; D003907:Dexamethasone; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D015577:Geriatric Assessment; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D008137:Longitudinal Studies; D008297:Male; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D012720:Severity of Illness Index
D003907:Dexamethasone; D006854:Hydrocortisone